ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1530G>T (p.Gln510His)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001798 SCV001159456 pathogenic not specified 2019-02-20 criteria provided, single submitter clinical testing The PTPN11 c.1530G>T; p.Gln510His variant (rs397507550) is reported in the literature in two unrelated fetuses with prenatal symptoms of Noonan syndrome, and it was not observed in the parents of either affected fetus, indicating a de novo origin (Gezdirici 2017). Additionally, a variant giving rise to the same amino acid change (c.1530G>C; p.Gln510His) was observed in an individual affected with LEOPARD syndrome (Wakabayashi 2011). The c.1530G>T; p.Gln510His variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The glutamine at codon 510 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, other amino acid substitutions at this codon (Arg, Glu, and Pro) have been reported in individuals with Noonan syndrome or LEOPARD syndrome and are considered pathogenic (Aoki 2008, Carcavilla 2013, Ganigara 2011, Wakabayashi 2011). Based on available information, the p.Gln510His variant is considered to be pathogenic. References: Aoki Y et al. The RAS/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders. Hum Mutat. 2008 Aug;29(8):992-1006. Carcavilla A et al. LEOPARD syndrome: a variant of Noonan syndrome strongly associated with hypertrophic cardiomyopathy. Rev Esp Cardiol (Engl Ed). 2013 May;66(5):350-6. Ganigara M et al. LEOPARD syndrome in an infant with severe hypertrophic cardiomyopathy and PTPN11 mutation. Ann Pediatr Cardiol. 2011 Jan;4(1):74-6. Gezdirici A et al. How necessary is to analyze PTPN11 gene in fetuses with first trimester cystic hygroma and normal karyotype? J Matern Fetal Neonatal Med. 2017 Apr;30(8):938-941. Wakabayashi Y et al. Implantable cardioverter defibrillator for progressive hypertrophic cardiomyopathy in a patient with LEOPARD syndrome and a novel PTPN11 mutation Gln510His. Am J Med Genet A. 2011 Oct;155A(10):2529-33.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001171895 SCV001334787 pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing
Service de Génétique Moléculaire,Hôpital Robert Debré RCV001261024 SCV001438421 likely pathogenic Noonan syndrome no assertion criteria provided clinical testing

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